rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2015-308-311rsp-2094Research ArticleОБЗОРREVIEWНовые возможности контроля эффективности метотрексата при ревматоидном артритеNEW POSSIBILITIES FOR MONITORING METHOTREXATE EFFICACY IN RHEUMATOID ARTHRITISМуравьевЮ. В.MuravyevYu. V.murawyu@mail.ruФГБНУ Научно-исследовательский институт ревматологии им. В.А. Насоновой, Москва, Россия 115522 Москва, Каширское шоссе, 34АРоссияV.A. Nasonova Research Institute of Rheumatology, Moscow, Russia 34A, Kashirskoe Shosse, Moscow 115522Russian Federation201509092015533308311Copyright © Муравьев Ю.В., 20152015Муравьев Ю.В.Muravyev Y.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/2094

Обзор посвящен прогнозированию лечебного эффекта метотрексата при ревматоидном артрите с помощью определения его уровня в эритроцитах

The review deals with the prediction of the therapeutic effect of methotrexate in rheumatoid arthritis, by determining its level in the red blood cells.

метотрексатревматоидный артритполиглютаматыпериод полувыведенияэритроцитыmethotrexaterheumatoid arthritispolyglutamateselimination half-lifered blood cellsReferencesНасонов ЕЛ. Метотрексат: перспективы применения в ревматологии. Москва: Филоматис; 2005. 200 с. [Nasonov EL. Metotreksat: perspektivy primeneniya v evmatologii [Methotrexate: prospects of application in rheumatology]. Moscow: Filomatis; 2005. 200 p.].Насонов ЕЛ. Метотрексат: перспективы применения в ревматологии. Москва: Филоматис; 2005. 200 с. [Nasonov EL. Metotreksat: perspektivy primeneniya v evmatologii [Methotrexate: prospects of application in rheumatology]. Moscow: Filomatis; 2005. 200 p.].Kay J, Westhovens R. Methotrexate: the gold standard without standardization. Ann Rheum Dis. 2009;68:1081–2. doi: 10.1136/ard.2008.102822Kay J, Westhovens R. Methotrexate: the gold standard without standardization. Ann Rheum Dis. 2009;68:1081–2. doi: 10.1136/ard.2008.102822Pincus T, Yazici Y, Sokka T, et al. Methotrexate as the «anchor drug» for the treatment of early rheumatoid arthritis. Clin Exp Rheumatol. 2003;21:179–85.Pincus T, Yazici Y, Sokka T, et al. Methotrexate as the «anchor drug» for the treatment of early rheumatoid arthritis. Clin Exp Rheumatol. 2003;21:179–85.Strand V, Cohen S, Schiff M, et al. Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Leflunomide Rheumatoid Arthritis Investigators Group. Arch Intern Med. 1999;159:2542–50. doi: 10.1001/archinte.159.21.2542Strand V, Cohen S, Schiff M, et al. Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Leflunomide Rheumatoid Arthritis Investigators Group. Arch Intern Med. 1999;159:2542–50. doi: 10.1001/archinte.159.21.2542Wessels JA, van der Kooij SM, le Cessie S, et al. A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent-onset rheumatoid arthritis. Arthritis Rheum. 2007;56:1765–75. doi: 10.1002/art.22640Wessels JA, van der Kooij SM, le Cessie S, et al. A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent-onset rheumatoid arthritis. Arthritis Rheum. 2007;56:1765–75. doi: 10.1002/art.22640Муравьев ЮВ. Вопросы стандартизации применения метотрексата в ежедневной практике ревматолога (обзор). Терапевтический архив. 2011;(5):33–7 [Murav'ev YuV. Questions of standardization of methotrexate in the daily practice of a rheumatologist (a review). Terapevticheskii arkhiv. 2011;(5):33–7 (In Russ.)].Муравьев ЮВ. Вопросы стандартизации применения метотрексата в ежедневной практике ревматолога (обзор). Терапевтический архив. 2011;(5):33–7 [Murav'ev YuV. Questions of standardization of methotrexate in the daily practice of a rheumatologist (a review). Terapevticheskii arkhiv. 2011;(5):33–7 (In Russ.)].Муравьев ЮВ, Евлоева НВ, Лебедева ВВ, Насонов ЕЛ. Современная практика лечения метотрексатом ревматоидного артрита. Научно-практическая ревматология. 2012;50(4):117–9 [Murav'ev YuV, Evloeva NV, Lebedeva VV, Nasonov EL. The modern practice of methotrexate treatment of rheumatoid arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2012;50(4):117–9 (In Russ.)].Муравьев ЮВ, Евлоева НВ, Лебедева ВВ, Насонов ЕЛ. Современная практика лечения метотрексатом ревматоидного артрита. Научно-практическая ревматология. 2012;50(4):117–9 [Murav'ev YuV, Evloeva NV, Lebedeva VV, Nasonov EL. The modern practice of methotrexate treatment of rheumatoid arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2012;50(4):117–9 (In Russ.)].Муравьев ЮВ. Дозирование метотрексата при лечении ревматоидного артрита. Научно-практическая ревматология. 2013;51(4):456–9 [Murav'ev YuV. Dosage of methotrexate in the treatment of rheumatoid arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2013;51(4):456–9 (In Russ.)].Муравьев ЮВ. Дозирование метотрексата при лечении ревматоидного артрита. Научно-практическая ревматология. 2013;51(4):456–9 [Murav'ev YuV. Dosage of methotrexate in the treatment of rheumatoid arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2013;51(4):456–9 (In Russ.)].Furst DE, Koehnke R, Burmeister LF, et al. Increasing methotrexate effect with increasing dose in the treatment of resistant rheumatoid arthritis. J Rheumatol. 1989;16(3):313-20.Furst DE, Koehnke R, Burmeister LF, et al. Increasing methotrexate effect with increasing dose in the treatment of resistant rheumatoid arthritis. J Rheumatol. 1989;16(3):313-20.Bannwarth B, Pehourcq F, Schaeverbeke T, Dehais J. Clinical pharmacokinetics of low-dose pulse methotrexate in rheumatoid arthritis. Clin Pharmacokinet. 1996;30:194–210. doi: 10.2165/00003088-199630030-00002Bannwarth B, Pehourcq F, Schaeverbeke T, Dehais J. Clinical pharmacokinetics of low-dose pulse methotrexate in rheumatoid arthritis. Clin Pharmacokinet. 1996;30:194–210. doi: 10.2165/00003088-199630030-00002Baggott JE, Morgan SL. Methotrexate catabolism to 7-hydroxymethotrexate in rheumatoid arthritis alters drug efficacy and retention and is reduced by folic acid supplementation. Arthritis Rheum. 2009 Aug;60(8):2257–61. doi: 10.1002/art.24685Baggott JE, Morgan SL. Methotrexate catabolism to 7-hydroxymethotrexate in rheumatoid arthritis alters drug efficacy and retention and is reduced by folic acid supplementation. Arthritis Rheum. 2009 Aug;60(8):2257–61. doi: 10.1002/art.24685Dervieux T, Furst D, Lein DO, et al. Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum. 2004;50:2766–74. doi: 10.1002/art.20460Dervieux T, Furst D, Lein DO, et al. Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum. 2004;50:2766–74. doi: 10.1002/art.20460Dervieux T, Zablocki R, Kremer J. Red blood cell methotrexate polyglutamates emerge as a function of dosage intensity and route of administration during pulse methotrexate therapy in rheumatoid arthritis. Rheumatology. 2010;49:2337–45. doi: 10.1093/rheumatology/keq216Dervieux T, Zablocki R, Kremer J. Red blood cell methotrexate polyglutamates emerge as a function of dosage intensity and route of administration during pulse methotrexate therapy in rheumatoid arthritis. Rheumatology. 2010;49:2337–45. doi: 10.1093/rheumatology/keq216Angelis-Stoforidis P, Vajda FJ, Christophidis N. Methotrexate polyglutamate levels in circulating erythrocytes and polymorphs correlate with clinical efficacy in rheumatoid arthritis. Clin Exp Rheumatol. 1999;17:313–20.Angelis-Stoforidis P, Vajda FJ, Christophidis N. Methotrexate polyglutamate levels in circulating erythrocytes and polymorphs correlate with clinical efficacy in rheumatoid arthritis. Clin Exp Rheumatol. 1999;17:313–20.Kremer JM, Lee JK. The safety and efficacy of the use of methotrexate in long-term therapy for rheumatoid arthritis. Arthritis Rheum. 1986;29:822–31. doi: 10.1002/art.1780290702Kremer JM, Lee JK. The safety and efficacy of the use of methotrexate in long-term therapy for rheumatoid arthritis. Arthritis Rheum. 1986;29:822–31. doi: 10.1002/art.1780290702Hroch M, Tukova J, Dolezalova P, Chladek J. An improved high-performance liquid chromatography method for quantification of methotrexate polyglutamates in red blood cells of children with juvenile idiopathic arthritis. Biopharm Drug Dispos. 2009;30:138–48. doi: 10.1002/bdd.654Hroch M, Tukova J, Dolezalova P, Chladek J. An improved high-performance liquid chromatography method for quantification of methotrexate polyglutamates in red blood cells of children with juvenile idiopathic arthritis. Biopharm Drug Dispos. 2009;30:138–48. doi: 10.1002/bdd.654Becker ML, Gaedigk R, van Haandel L, et al. The effect of genotype on methotrexate polyglutamate variability in juvenile idiopathic arthritis and association with drug response. Arthritis Rheum. 2011;63:276–85. doi: 10.1002/art.30080Becker ML, Gaedigk R, van Haandel L, et al. The effect of genotype on methotrexate polyglutamate variability in juvenile idiopathic arthritis and association with drug response. Arthritis Rheum. 2011;63:276–85. doi: 10.1002/art.30080Becker ML, van Haandel L, Gaedigk R, et al. Analysis of intracellular methotrexate polyglutamates in patients with juvenile idiopathic arthritis: effect of route of administration on variability in intracellular methotrexate polyglutamate concentrations. Arthritis Rheum. 2010;62:1803–12. doi: 10.1002/art.27434Becker ML, van Haandel L, Gaedigk R, et al. Analysis of intracellular methotrexate polyglutamates in patients with juvenile idiopathic arthritis: effect of route of administration on variability in intracellular methotrexate polyglutamate concentrations. Arthritis Rheum. 2010;62:1803–12. doi: 10.1002/art.27434Goldman ID. The characteristics of the membrane transport of amethopterin and the naturally occurring folates. Ann N Y Acad Sci. 1971;186:400–22. doi: 10.1111/j.1749-6632.1971.tb46996.xGoldman ID. The characteristics of the membrane transport of amethopterin and the naturally occurring folates. Ann N Y Acad Sci. 1971;186:400–22. doi: 10.1111/j.1749-6632.1971.tb46996.xWesterhof GR, Schornagel JH, Kathmann I, et al. Carrier- and receptor-mediated transport of folate antagonists targeting folate-dependent enzymes:correlates of molecular structure and biological activity. Mol Pharmacol. 1995;48:459–71.Westerhof GR, Schornagel JH, Kathmann I, et al. Carrier- and receptor-mediated transport of folate antagonists targeting folate-dependent enzymes:correlates of molecular structure and biological activity. Mol Pharmacol. 1995;48:459–71.Jansen G, Mauritz R, Drori S, et al. A structurally altered human reduced folate carrier with increased folic acid transport mediates a novel mechanism of antifolate resistance. J Biol Chem. 1998;273:189–98. doi: 10.1074/jbc.273.46.30189Jansen G, Mauritz R, Drori S, et al. A structurally altered human reduced folate carrier with increased folic acid transport mediates a novel mechanism of antifolate resistance. J Biol Chem. 1998;273:189–98. doi: 10.1074/jbc.273.46.30189Jansen G, Pieters R. The role of impaired transport in (pre)clinical resistance to methotrexate: insights on new antifolates. Drug Resist Updat. 1998;1(3):211–8. doi: 10.1016/S1368-7646(98)80042-3Jansen G, Pieters R. The role of impaired transport in (pre)clinical resistance to methotrexate: insights on new antifolates. Drug Resist Updat. 1998;1(3):211–8. doi: 10.1016/S1368-7646(98)80042-3Rots MG, Pieters R, Kaspers GJ, et al. Classification of ex vivo methotrexate resistance in acute lymphoblastic and myeloid leukaemia. Br Haematol. 2000;110:791–800. doi: 10.1046/j.1365-2141.2000.02070.xRots MG, Pieters R, Kaspers GJ, et al. Classification of ex vivo methotrexate resistance in acute lymphoblastic and myeloid leukaemia. Br Haematol. 2000;110:791–800. doi: 10.1046/j.1365-2141.2000.02070.xChabner BA, Allegra CJ, Curt GA, et al. Polyglutamation of methotrexate. Is methotrexate a prodrug? J Clin Invest. 1985;76(3):907–12. Review. doi: 10.1172/JCI112088Chabner BA, Allegra CJ, Curt GA, et al. Polyglutamation of methotrexate. Is methotrexate a prodrug? J Clin Invest. 1985;76(3):907–12. Review. doi: 10.1172/JCI112088Kremer JM. Still trying to understand methotrexate. J Rheumatol. 2014;41(11):2099–101. doi: 10.3899/jrheum.141081Kremer JM. Still trying to understand methotrexate. J Rheumatol. 2014;41(11):2099–101. doi: 10.3899/jrheum.141081Dalrymple JM, Stamp LK, O'Donnell JL, et al. Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis. Arthritis Rheum. 2008;58:3299–308. doi: 10.1002/art.24034Dalrymple JM, Stamp LK, O'Donnell JL, et al. Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis. Arthritis Rheum. 2008;58:3299–308. doi: 10.1002/art.24034Weinblatt ME, Trentham DE, Fraser PA, et al. Long-term prospective trial of low-dose methotrexate in rheumatoid arthritis. Arthritis Rheum. 1988;31:167–75. doi: 10.1002/art.1780310203Weinblatt ME, Trentham DE, Fraser PA, et al. Long-term prospective trial of low-dose methotrexate in rheumatoid arthritis. Arthritis Rheum. 1988;31:167–75. doi: 10.1002/art.1780310203Dervieux T, Furst D, Lein DO, et al. Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate: results of a multicentred cross sectional observational study. Ann Rheum Dis. 2005;64:1180–5. doi: 10.1136/ard.2004.033399Dervieux T, Furst D, Lein DO, et al. Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate: results of a multicentred cross sectional observational study. Ann Rheum Dis. 2005;64:1180–5. doi: 10.1136/ard.2004.033399Cronstein BN. Going with flow: methotrexate, adenosine, and blood flow. Ann Rheum Dis. 2006;65:421–2. doi: 10.1136/ard.2005.049601Cronstein BN. Going with flow: methotrexate, adenosine, and blood flow. Ann Rheum Dis. 2006;65:421–2. doi: 10.1136/ard.2005.049601Riksen NP, Barrera P, van den Broek PH, et al. Methotrexat modulates the kinetics of adenosine in humans in vivo. Ann Rheum Dis. 2006;65:466–70. doi: 10.1136/ard.2005.048637Riksen NP, Barrera P, van den Broek PH, et al. Methotrexat modulates the kinetics of adenosine in humans in vivo. Ann Rheum Dis. 2006;65:466–70. doi: 10.1136/ard.2005.048637Dervieux T, Greenstein N, Kremer J. Pharmacogenetic andmetabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis. Arthritis Rheum. 2006;54:3095–103. doi: 10.1002/art.22129Dervieux T, Greenstein N, Kremer J. Pharmacogenetic andmetabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis. Arthritis Rheum. 2006;54:3095–103. doi: 10.1002/art.22129Baggott JE, Vaughn WH, Hudson BB. Inhibition of 5-aminoimidazole-4-carboxamide ribotide transformylase, adenosine deaminase and 5'-adenylate deaminase by olyglutamates of methotrexate and oxidized folates and by 5-aminoimidazole- 4-carboxamide riboside and ribotide. Biochem J. 1986;236(1):193–200.Baggott JE, Vaughn WH, Hudson BB. Inhibition of 5-aminoimidazole-4-carboxamide ribotide transformylase, adenosine deaminase and 5'-adenylate deaminase by olyglutamates of methotrexate and oxidized folates and by 5-aminoimidazole- 4-carboxamide riboside and ribotide. Biochem J. 1986;236(1):193–200.Allegra CJ, Drake JC, Jolivet J, Chabner BA. Inhibition of phosphoribosyl aminoimidazole carboxamide transformylase by methotrexate and dihydrofolic acid polyglutamates. Proc Natl Acad Sci USA. 1985;82(15):4881–5. doi: 10.1073/pnas.82.15.4881Allegra CJ, Drake JC, Jolivet J, Chabner BA. Inhibition of phosphoribosyl aminoimidazole carboxamide transformylase by methotrexate and dihydrofolic acid polyglutamates. Proc Natl Acad Sci USA. 1985;82(15):4881–5. doi: 10.1073/pnas.82.15.4881Stamp LK, O'Donnell JL, Chapman PT, et al. Determinants of red blood cell methotrexate polyglutamate concentrations in rheumatoid arthritis patientsreceiving long-term methotrexate treatment. Arthritis Rheum. 2009;60:2248–56. doi: 10.1002/art.24653Stamp LK, O'Donnell JL, Chapman PT, et al. Determinants of red blood cell methotrexate polyglutamate concentrations in rheumatoid arthritis patientsreceiving long-term methotrexate treatment. Arthritis Rheum. 2009;60:2248–56. doi: 10.1002/art.24653Hobl EL, Jilma B, Erlacher L, et al. A short-chain methotrexate polyglutamate as outcome parameter in rheumatoid arthritis patients receiving methotrexate. Clin Exp Rheumatol. 2011 Dec 7. [Epub ahead of print].Hobl EL, Jilma B, Erlacher L, et al. A short-chain methotrexate polyglutamate as outcome parameter in rheumatoid arthritis patients receiving methotrexate. Clin Exp Rheumatol. 2011 Dec 7. [Epub ahead of print].Kremer JM, Rynes RI, Bartholomew LE. Severe flare of rheumatoid arthritis after discontinuation of long-term methotrexate therapy. Double-blind study. Am J Med. 1987;82(4):781–6. doi: 10.1016/0002-9343(87)90015-5Kremer JM, Rynes RI, Bartholomew LE. Severe flare of rheumatoid arthritis after discontinuation of long-term methotrexate therapy. Double-blind study. Am J Med. 1987;82(4):781–6. doi: 10.1016/0002-9343(87)90015-5Stamp LK, O'Donnell JL, Chapman PT, et al. Determinants of red blood cell methotrexate polyglutamate concentrations in rheumatoid arthritis patients receiving long-term methotrexate treatment. Arthritis Rheum. 2009;60(8):2248–56. doi: 10.1002/art.24653Stamp LK, O'Donnell JL, Chapman PT, et al. Determinants of red blood cell methotrexate polyglutamate concentrations in rheumatoid arthritis patients receiving long-term methotrexate treatment. Arthritis Rheum. 2009;60(8):2248–56. doi: 10.1002/art.24653Stamp LK, Barclay ML, O'Donnell JL, et al. Effects of changing from oral to subcutaneous methotrexate on red blood cell methotrexate polyglutamate concentrations and disease activity in patients with rheumatoid arthritis. J Rheumatol. 2011;38(12):2540–7. doi: 10.3899/jrheum.110481Stamp LK, Barclay ML, O'Donnell JL, et al. Effects of changing from oral to subcutaneous methotrexate on red blood cell methotrexate polyglutamate concentrations and disease activity in patients with rheumatoid arthritis. J Rheumatol. 2011;38(12):2540–7. doi: 10.3899/jrheum.110481Stamp LK, Barclay M. Therapeutic drug monitoring in rheumatic diseases: utile or futile? Rheumatology (Oxford). 2014;53(6):988–97. doi: 10.1093/rheumatology/ket355Stamp LK, Barclay M. Therapeutic drug monitoring in rheumatic diseases: utile or futile? Rheumatology (Oxford). 2014;53(6):988–97. doi: 10.1093/rheumatology/ket355Pan S, Stamp LK, Duffull SB, et al. Assessment of the relationship between methotrexate polyglutamates in red blood cells and clinical response in patients commencing methotrexate for rheumatoid arthritis. Clin Pharmacokinet. 2014;53(12):1161–70. doi: 10.1007/s40262-014-0179-5Pan S, Stamp LK, Duffull SB, et al. Assessment of the relationship between methotrexate polyglutamates in red blood cells and clinical response in patients commencing methotrexate for rheumatoid arthritis. Clin Pharmacokinet. 2014;53(12):1161–70. doi: 10.1007/s40262-014-0179-5

The authors declare that there are no conflicts of interest present.